Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me-EBP50 KO, and blebbistatin treatment potentiated the effects of Me-EBP50 KO. In OCCC cells from clinical samples, Me-EBP50 and MYH9 were co-localized at the apical plasma membrane. Patients with a combination of Me-EBP50-high and MYH9-high scores had the best prognosis for overall and progression-free survival. Our data suggest that Me-EBP50 has tumor-suppressive effects through the establishment and maintenance of epithelial polarization. By contrast, loss of Me-EBP50 expression induces EMT-like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC-like properties, which in turn promote OCCC progression.
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http://dx.doi.org/10.1002/1878-0261.13503 | DOI Listing |
Int J Mol Sci
January 2025
Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.
From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca transfers. In addition, from around the eighth week of gestation, increasing amounts of calcium must be routed directly from maternal blood to the foetus for bone mineralisation through a flow-through system, which does not impact the intracellular Ca concentration.
View Article and Find Full Text PDFElife
April 2024
Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Cancers (Basel)
December 2023
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Kanagawa, Japan.
Ezin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that interacts with several partner molecules including β-catenin. Here, we examined the crosstalk between EBP50 and nuclear catenin during colorectal carcinoma (CRC) progression. In clinical samples, there were no correlations between the subcellular location of EBP50 and any clinicopathological factors.
View Article and Find Full Text PDFTransl Androl Urol
August 2023
Department of Pathology and Translational Pathobiology, LSU Health Shreveport, Shreveport, LA, USA.
Background: Na/H exchanger (NHE) maintains the alkaline pH of epithelial cells working at the cellular membrane and exchanging H/Na ions. In renal tubular epithelial cells, the reabsorption of NaCl is implemented by NHE3 isoform, which is regulated by NHE regulatory factor-1 (NHERF1). Normally situated at the apical zones of proximal tubular cells, NHERF1 participates in cytoskeletal reorganization and signal transduction facilitating structural stability and ion exchange.
View Article and Find Full Text PDFMol Oncol
October 2023
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan.
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9).
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